1. Field of the Invention
This invention relates to a new method of treatment for patients, i.e. men having benign prostatic hyperplasia (BPH), involving combination therapy of administering therapeutically effective amounts of a 5.alpha.-reductase inhibitor in combination with an .alpha..sub.1 -adrenergic receptor blocker.
2. Background of the Invention
Benign prostatic hyperplasia (BPH) affects a substantial number of males over the age of 50 and usually requires surgery in advanced stages for relief.
It is known that testosterone (T) is secreted by the testes and adrenal glands but can undergo a 5.alpha.-reductase mediated conversion to dihydrotestosterone (DHT) in peripheral sites including the liver, skin, and prostate. DHT is preferentially bound by the nucleus of prostatic cells thus indicating that DHT, rather than T, is the primary androgen required by the prostate for its growth and function. This led to the hypothesis that, by inhibiting 5.alpha.-reductase, the formation of DHT could be curtailed and hopefully prostate regression obtained.
Finasteride, 17.beta.(N-t-butyl)carbamoyl-4-aza-5.alpha.-androst-1-en-3-one, was developed as a compound which was found to inhibit 5.alpha.-reductase and exhibit positive effects against benign prostatic hyperplasia. Finasteride is a 4-azasteroid and a competitive, inhibitor of the enzyme. It shows no affinity for the androgen receptor and so would not be expected to interfere with the binding and action of T in those tissues, such as muscle, which respond to T, and thus should not result in feminizing characteristics.
Typical 4-aza steroid 5.alpha.-reductase inhibitors include those developed by Merck. (See U.S. Pat. No. 4,377,584 to Rasmusson, et al.; U.S. Pat. No. 4,220,735 to Rasmusson, et al.; U.S. Pat. No. 4,845,104 to Carlin, et al.; U.S. Pat. No. 4,760,071 to Rasmusson, et al., which discloses finasteride, being 17.beta.-(N-t-butyl)carbamoyl-4-aza-5.alpha.-androst-1-en-3-one, known by its trademark as PROSCAR*; U.S. Pat. No. 4,732,897 to Cainelli, et al.; U.S. Pat. No. 4,859,681 to Rasmusson, et al.; EPO Publn. 0 155 076; EPO Publn. 0 004 949; and EPO Publn. 0 314 189.
In many instances, reversal of the prostate enlargement process is accompanied by symptomatic relief from nocturia, hesitancy, and difficulty in urination. However, symptomatic relief does not occur in all cases. When the 5.alpha.-reductase inhibitor inhibits the rate of development of the enlarged prostate without attendant shrinkage, symptomatic relief as experienced by the patients may not occur.
What is desired in the art is a combination therapy both to treat the underlying cause of BPH and to treat the short-term symptoms of the disease as well.